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TGF? receptor signaling is essential for inflammation-induced but not ?-cell workload-induced ?-cell proliferation.


ABSTRACT: Protection and restoration of a functional ?-cell mass are fundamental strategies for prevention and treatment of diabetes. Consequently, knowledge of signals that determine the functional ?-cell mass is of immense clinical relevance. Transforming growth factor ? (TGF?) superfamily signaling pathways play a critical role in development and tissue specification. Nevertheless, the role of these pathways in adult ?-cell homeostasis is not well defined. Here, we ablated TGF? receptor I and II genes in mice undergoing two surgical ?-cell replication models (partial pancreatectomy or partial duct ligation), representing two triggers for ?-cell proliferation, increased ?-cell workload and local inflammation, respectively. Our data suggest that TGF? receptor signaling is necessary for baseline ?-cell proliferation. By either provision of excess glucose or treatment with exogenous insulin, we further demonstrated that inflammation and increased ?-cell workload are both stimulants for ?-cell proliferation but are TGF? receptor signaling dependent and independent, respectively. Collectively, by using a pancreas-specific TGF? receptor-deleted mouse model, we have identified two distinct pathways that regulate adult ?-cell proliferation. Our study thus provides important information for understanding ?-cell proliferation during normal growth and in pancreatic diseases.

SUBMITTER: Xiao X 

PROVIDER: S-EPMC3609557 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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TGFβ receptor signaling is essential for inflammation-induced but not β-cell workload-induced β-cell proliferation.

Xiao Xiangwei X   Wiersch John J   El-Gohary Yousef Y   Guo Ping P   Prasadan Krishna K   Paredes Jose J   Welsh Carey C   Shiota Chiyo C   Gittes George K GK  

Diabetes 20121217 4


Protection and restoration of a functional β-cell mass are fundamental strategies for prevention and treatment of diabetes. Consequently, knowledge of signals that determine the functional β-cell mass is of immense clinical relevance. Transforming growth factor β (TGFβ) superfamily signaling pathways play a critical role in development and tissue specification. Nevertheless, the role of these pathways in adult β-cell homeostasis is not well defined. Here, we ablated TGFβ receptor I and II genes  ...[more]

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